Abstract: Understanding how genetic and environmental factors impact drug use and abuse may be critical for addiction prevention and diagnosis, as well as the development of novel effective addiction therapeutics. This application plans to provide 3 predoctoral training slots (for ~2 yrs, starting in the 2nd yr) in the Weill Cornell Graduate School (WCGS) Neuroscience and Pharmacology Programs aimed at understanding the impact of genes and environment on drug addiction. A unique feature of this training plan is the diversity of faculty expertise in both genetic (e.g. sex, single nucleotide polymorphisms, gene splice variants, dendritic/axonal translation, and epigenetics) and environmental (maternal environment, developmental stage, and stress) factors that are essential for the emergence of addictive disease. Our faculty is also noteworthy for the breadth of the approaches they bring to addiction science; we have expertise in studying how several major abused drugs (i.e. opiates, cocaine, and other psychostimulants) impact neuronal function from the expression and behavior of single molecules to the performance of complex functional systems that regulate the behavior of rodents and humans. In addition to our talented faculty, this training grant will take advantage of the WCGS outstanding research environment, educational resources, and recruiting activities, particularly our history of attracting and training under-represented minorities as basic and clinical scientists. Particular strengths of the training grant include: 1) the experience of the Director and Co-Director in mentoring, teaching and drug abuse research; 2) the broad scope of multidisciplinary research training provided by the faculty; 3) extensive collaborations and co-mentoring between the faculty; and 4) the strong emphasis on ?bench-to- bedside? translational research. Training grant faculty will be divided into three groups: 1) Major Sponsors: graduate student thesis mentors with NIDA mission supported research programs; 2) Training Sponsors: individuals with extensive experience in drug abuse research who will work closely with Major Sponsors and their trainees; and 3) Minor Sponsors: individuals with NIDA- mission interests who will collaborate with Major Sponsors and their trainees. Resource Cores comprised of training grant faculty from all three groups will be established to provide a platform for students to incorporate approaches from multiple laboratories into their PhD thesis work. Beyond the laboratory, a new course entitled ?Addiction and Society? developed by a group of graduate students in consultation with faculty, as well as a Drug Abuse focused retreat and WCGS developed programs in grant-preparation, will provide students with important training experiences in teaching, grantsmanship, and networking that will be essential for their career development. These courses together with the existing coursework and curricula, symposia and lectures, as well as each students individual training plan, will provide a solid foundation for the development of independent basic and clinical scientists in drug abuse research.